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Clinical Trial Results:
A 24-week, Phase IIB, Randomized, Controlled, Parallel group, Multi-center Study to Evaluate the Safety and Efficacy of GSK1278863 in Subjects with Anemia Associated with Chronic Kidney Diseases who are not on Dialysis.

Summary
EudraCT number	2013-002681-39
Trial protocol	ES SE GB CZ HU DK
Global end of trial date	14 May 2015

Results information
Results version number	v2(current)
This version publication date	04 Jan 2017
First version publication date	15 May 2016
Other versions	v1
Version creation reason	Correction of full data set minor changes made to OM descriptions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

113747

ISRCTN number

US NCT number

NCT01977573

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Middlesex, Brentford, United Kingdom,

Public contact

GlaxoSmithKline, GlaxoSmithKline, +1 8664357343,

Scientific contact

GlaxoSmithKline, GlaxoSmithKline, +1 8664357343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 Aug 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 May 2015

Was the trial ended prematurely?

Main objective of the trial

This study will be conducted in approximately 228 subjects with anemia associated with CKD who are not on dialysis. Two groups of subjects will be enrolled into the study: Group 1: recombinant human erythropoietin (rhEPO) naive subjects; Group 2: rhEPO users, who are currently receiving rhEPO. Subjects who are rhEPO naive will be randomized to receive either GSK1278863 once daily (QD) or rhEPO in a 3:1 fashion; subjects who are receiving an rhEPO before enrolling (rhEPO users) will be randomized in a 1:1 fashion to GSK1278863 QD or to the control arm. For those randomized to the control arm, the decision around whether the subject requires rhEPO, the selection of the type of rhEPO (if needed) and the choice of rhEPO dose to achieve and maintain Hgb concentrations within the target range should be based on Investigator clinical judgment, with the historical rhEPO dose and the current Hgb value being considered.

Protection of trial subjects

Background therapy

Evidence for comparator

Actual start date of recruitment

31 Oct 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 8

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

Czech Republic: 20

Country: Number of subjects enrolled

Denmark: 3

Country: Number of subjects enrolled

France: 7

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Hungary: 6

Country: Number of subjects enrolled

Korea, Republic of: 19

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Russian Federation: 38

Country: Number of subjects enrolled

Spain: 24

Country: Number of subjects enrolled

Sweden: 5

Country: Number of subjects enrolled

United Kingdom: 7

Country: Number of subjects enrolled

United States: 45

Country: Number of subjects enrolled

Japan: 42

Worldwide total number of subjects

252

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

149

85 years and over

Subject disposition

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Recruitment details

Two groups of participants (par.) were enrolled in this study. Group 1 consisted of recombinant human erythropoietin (rhEPO)-naive par. whereas Group 2 consisted of rhEPO users.

Screening details

Post screening, eligible par. were randomized to receive either GSK1278863 once a day (QD) or to the Control arm in a 3:1 fashion in Group 1 and 1:1 fashion in Group 2.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

rhEPO-Naive GSK1278863

Arm description

RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.

Arm type

Experimental

Investigational medicinal product name

GSK1278863 tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GSK1278863 once daily for 24 weeks and were blinded to the dose-level they received throughout the study. Blinding was maintained by providing the required dose in an appropriate combination of GSK1278863 and/or placebo tablets.

Investigational medicinal product name

Placebo to match GSK1278863 tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

rhEPO-Naive Control

Arm description

RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator’s clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.

Arm type

Active comparator

Investigational medicinal product name

Standard of care including RhEPO if needed

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Cutaneous use, Intravenous use

Dosage and administration details

Standard of care provided accordingly.

rhEPO-User GSK1278863

Arm description

RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason [based on Investigator’s opinion] to start rhEPO therapy).

Arm type

Experimental

Investigational medicinal product name

GSK1278863 tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Placebo to match GSK1278863 tablet

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

rhEPO-User Control

Arm description

RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.

Arm type

Active comparator

Investigational medicinal product name

Stardard of care include RhEPO if needed

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Cutaneous use, Intravascular use

Dosage and administration details

Standard of care provided accordingly.

Number of subjects in period 1	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Started	136	44	36	36
Completed	116	41	32	33
Not completed	20	3	4	3
Physician decision	1	-	-	-
Consent withdrawn by subject	6	1	1	1
Adverse event, non-fatal	7	-	2	1
Lost to follow-up	1	-	-	1
Protocol deviation	3	1	-	-
reached defined stopping criteria	2	1	-	-
Protocol-Defined Stopping Criteria	-	-	1	-

Baseline characteristics

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Reporting group title

rhEPO-Naive GSK1278863

Reporting group description

Reporting group title

rhEPO-Naive Control

Reporting group description

Reporting group title

rhEPO-User GSK1278863

Reporting group description

Reporting group title

rhEPO-User Control

Reporting group description

Reporting group values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control	Total
Number of subjects	136	44	36	36	252
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	67.7 ± 12.39	64.5 ± 14.11	61.9 ± 14.65	66.7 ± 12.89	-
Gender categorical
Units: Subjects
Female	56	20	17	13	106
Male	80	24	19	23	146
Race, customized
Units: Subjects
White	89	30	25	19	163
African American	14	2	2	4	22
Asian	33	12	9	13	67

End points

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Reporting group title

rhEPO-Naive GSK1278863

Reporting group description

Reporting group title

rhEPO-Naive Control

Reporting group description

Reporting group title

rhEPO-User GSK1278863

Reporting group description

Reporting group title

rhEPO-User Control

Reporting group description

Primary: Summary of hemoglobin (Hgb) concentration at Week 24

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End point title

Summary of hemoglobin (Hgb) concentration at Week 24 ^[1]

End point description

The original Hgb target range was 9.0 to 10.5 g/dL for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5. The amended Hgb target range was 10.0 to 11.5 g/dL for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. Intent-to-Treat (ITT): The ITT population consisted of all randomized participants who received at least one dose of study drug, had a Baseline and at least one corresponding on-treatment assessment. Only participants who were available at the indicated time point were analyzed.

End point type

Primary

End point timeframe

Week 24

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	123	43	33	36
Units: grams per deciliter
arithmetic mean (standard deviation)
Original n=45,15,19,13	10.2 ± 0.906	10.64 ± 0.664	10.03 ± 0.522	10.66 ± 0.62
Amended n=61,21,11,17	10.96 ± 1.044	11.05 ± 1.144	10.42 ± 0.827	10.86 ± 1.182

No statistical analyses for this end point

Secondary: Number of participants with hemoglobin (Hgb) in the target range at Week 24

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End point title

Number of participants with hemoglobin (Hgb) in the target range at Week 24

End point description

Target range is defined as: Original Hgb Criteria of 9.0 to 10.5 gram/deciliter (g/dL), and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. ITT population. Only participants who were available at the indicated time point were analyzed.

End point type

Secondary

End point timeframe

Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	106	36	30	30
Units: participants
number (not applicable)	78	20	22	19

No statistical analyses for this end point

Secondary: Number of participants reaching pre-defined Hgb stopping criteria

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End point title

Number of participants reaching pre-defined Hgb stopping criteria

End point description

The Hgb stopping criteria was a value of <7.5 mg/dL obtained on-site via a validated point-of-care Hgb measurement device, which necessitated permanent discontinuation of the study medication. None of the participants met the stopping criteria therefore there is no data to present for this outcome measure. ITT population.

End point type

Secondary

End point timeframe

Over a period of 24 Weeks

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	136	44	36	36
Units: Participants
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Percent change from Baseline in hepcidin concentration at Week 24

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End point title

Percent change from Baseline in hepcidin concentration at Week 24

End point description

Baseline is the last pre-dose hepcidin value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the Week 24 value. Intent-to-Treat (ITT) population consisted all randomized participants who received at least one dose of study drug, had a Baseline and at least one corresponding on-treatment assessment. Only participants with available hepcidin values at Baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	106	35	30	29
Units: percent change in Hepcidin
geometric mean (confidence interval 95%)	-19.27 (-28.1 to -9.36)	6.67 (-13.62 to 31.72)	-9.87 (-28.59 to 13.76)	-17.12 (-33.22 to 2.86)

No statistical analyses for this end point

Secondary: Maximum observed change from Baseline in serum erythropoietin (EPO)

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End point title

Maximum observed change from Baseline in serum erythropoietin (EPO)

End point description

Blood samples for control arm were collected pre-dose for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm . Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-baseline values minus the Baseline value.

End point type

Secondary

End point timeframe

Baseline to Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	123	42	33	36
Units: International Units per liter
arithmetic mean (standard deviation)	7.27 ± 12.744	27.05 ± 94.999	3.69 ± 20.554	25.85 ± 38.89

No statistical analyses for this end point

Secondary: Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)

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End point title

Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)

End point description

Blood samples for control arm were collected pre-dose for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for VEGF measurement. The maximum observed change from baseline in VEGF was recorded for each arm. Baseline value for VEGF is the pre-dose value on Day 1. Change from Baseline in VEGF was calculated as the individual post-baseline values minus the Baseline value.

End point type

Secondary

End point timeframe

Baseline and up to Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	123 ^[2]	42 ^[3]	33 ^[4]	3 ^[5]
Units: percent change in VEGF concentration
geometric mean (confidence interval 95%)	76.36 (59.46 to 95.06)	26.84 (1.73 to 58.15)	49.99 (28.28 to 75.39)	40.85 (19.14 to 66.52)

Notes
[2] - ITT population. Only pars with data available at Baseline and a maximum observed change analyzed
[3] - ITT population. Only pars with data available at Baseline and a maximum observed change analyzed
[4] - ITT population. Only pars with data available at Baseline and a maximum observed change analyzed
[5] - ITT population. Only pars with data available at Baseline and a maximum observed change analyzed6

No statistical analyses for this end point

Secondary: Percentage of time within, below, and above hemoglobin (Hgb) target range, between Weeks 12 and 24

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End point title

Percentage of time within, below, and above hemoglobin (Hgb) target range, between Weeks 12 and 24

End point description

The number of days a participant's Hgb was within target range was calculated by estimating (using linear interpolation) the number of days within target range between two scheduled Hgb visits. Percentage of time within range for a participant was calculated by dividing the total number of days that Hgb was within range during Weeks 12 to 24 by the total number of days the participant remained on treatment during Weeks 12 to 24. Similary, percent of time above and below Hgb target range was calculated. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. ITT population. Only participants with data available at specific time points were analyzed.

End point type

Secondary

End point timeframe

Weeks 12 to 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	112	38	30	32
Units: percentage of days
arithmetic mean (standard deviation)
Percentage of time within target range	68.99 ± 34.612	51.01 ± 41.403	75.06 ± 32.485	61.29 ± 43.352
Percentage of time above target range	22.84 ± 33.825	45.1 ± 42.579	17.96 ± 28.809	31.1 ± 41.683
Percentage of time below target range	8.17 ± 20.301	3.89 ± 16.175	6.98 ± 21.118	7.61 ± 25.113

No statistical analyses for this end point

Secondary: Change from Baseline in ferritin concentration at Week 24

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End point title

Change from Baseline in ferritin concentration at Week 24

End point description

Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value. ITT population. Only participants with data available at specific time point were analyzed. ITT population. Only participants with data available at specific time point were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	108	36	30	30
Units: micrograms per liter
arithmetic mean (standard deviation)	-30.8 ± 110.5	-2.4 ± 77.06	-63.4 ± 141.93	-20.4 ± 63.38

No statistical analyses for this end point

Secondary: Change from Baseline in transferrin concentration at Week 24

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End point title

Change from Baseline in transferrin concentration at Week 24

End point description

Baseline is the last pre-dose transferrin value. Change from Baseline in transferrin was calculated by subtracting the Baseline value from the Week 24 value. ITT population. Only participants with data available at specific time point were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	107	36	30	30
Units: grams per liter
arithmetic mean (standard deviation)	0.077 ± 0.3577	-0.008 ± 0.2694	0.171 ± 0.4124	0.018 ± 0.2395

No statistical analyses for this end point

Secondary: Percent change from Baseline in transferrin saturation at Week 24

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End point title

Percent change from Baseline in transferrin saturation at Week 24

End point description

Transferrin saturation is measured as a percentage; it is a ratio of serum iron and total iron-binding capacity. Baseline is the last pre-dose transferrin saturation value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the post-dose value. ITT population. Only participants with data available at specific time point were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	106	35	30	30
Units: percent change
geometric mean (confidence interval 95%)	-1.1 (-8 to 6.4)	12.3 (2.2 to 23.3)	-15.7 (-26.8 to -3)	11.4 (-14.7 to 45.6)

No statistical analyses for this end point

Secondary: Change from Baseline in total iron at Week 24

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End point title

Change from Baseline in total iron at Week 24

End point description

Baseline is the last pre-dose total iron value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value. ITT population. Only participants with available total iron values at Baseline and Week 24 were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	107	36	30	30
Units: micromoles per liter
arithmetic mean (standard deviation)	1 ± 5.01	2.5 ± 5.98	-1.8 ± 5.54	0.7 ± 8.36

No statistical analyses for this end point

Secondary: Change from Baseline in total iron binding capacity (TIBC) at Week 24

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End point title

Change from Baseline in total iron binding capacity (TIBC) at Week 24

End point description

TIBC measures the blood's capacity to bind iron with transferrin. Baseline is the last pre-dose TIBC value. Change from Baseline in TIBC was calculated by subtracting the Baseline value from the Week 24 value. ITT population. Only participants with data available at specific timepoint were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	106	35	30	30
Units: micromoles per liter
arithmetic mean (standard deviation)	3.2 ± 6.46	0.1 ± 5.17	3 ± 9.44	-1 ± 6.69

No statistical analyses for this end point

Secondary: Change from Baseline in reticulocyte hemoglobin (CHr) at Week 24

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End point title

Change from Baseline in reticulocyte hemoglobin (CHr) at Week 24

End point description

Reticulocytes are slightly immature red blood cells. Reticulocyte Hgb content is used to differentiate iron deficiency from other causes of anemia. Baseline is the last pre-dose CHr value. Change from Baseline in reticulocyte Hgb was calculated by subtracting the Baseline value from the post-dose value. ITT population. Only participants with data available at specific timepoint were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	108	35	30	30
Units: picogram
arithmetic mean (standard deviation)	-0.19 ± 1.109	-0.33 ± 1.085	-0.32 ± 0.864	-0.19 ± 1.546

No statistical analyses for this end point

Secondary: Change from Baseline in hematocrit at Week 24

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End point title

Change from Baseline in hematocrit at Week 24

End point description

Baseline is the last pre-dose hematocrit value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value. ITT population. Only participants with data available at specific timepoint were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	111	36	30	30
Units: percentage change in Fraction of 1
arithmetic mean (standard deviation)	2.64 ± 3.389	3.13 ± 3.245	-0.66 ± 3.074	2.09 ± 3.243

No statistical analyses for this end point

Secondary: Change from Baseline in red blood cell count at Week 24

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End point title

Change from Baseline in red blood cell count at Week 24

End point description

Baseline is the last pre-dose red blood cell count. Change from Baseline in red blood cell count was calculated by subtracting the Baseline count from the post-dose count.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	111 ^[6]	36 ^[7]	30 ^[8]	30 ^[9]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)	0.28 ± 0.377	0.34 ± 0.365	-0.08 ± 0.312	0.22 ± 0.318

Notes
[6] - ITT population. Only participants with data available at specific time point were analyzed.
[7] - ITT population. Only participants with data available at specific time point were analyzed.
[8] - ITT population. Only participants with data available at specific time point were analyzed.
[9] - ITT population. Only participants with data available at specific time point were analyzed.

No statistical analyses for this end point

Secondary: Change from Baseline in reticulocyte cell count at Week 24

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End point title

Change from Baseline in reticulocyte cell count at Week 24

End point description

Reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline is the last pre-dose red reticulocyte count. Change from Baseline in reticulocyte cell count was calculated by subtracting the Baseline count from the Week 24 count. ITT population. Only participants with data available at specific timepoint were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	111	36	30	31
Units: percentage of reticulocytes
arithmetic mean (standard deviation)	-0.02 ± 0.551	-0.12 ± 0.648	0.27 ± 0.892	-0.09 ± 0.755

No statistical analyses for this end point

Secondary: Concentration of GSK1278863 and relevant metabolites as a population pharmacokinetic endpoint

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End point title

Concentration of GSK1278863 and relevant metabolites as a population pharmacokinetic endpoint ^[10]

End point description

Blood samples were collected for individual plasma GSK1278863 and metabolite (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531401, and GSK2531403) concentration measurement on Day 1 (pre-dose), Wk 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose). Participants available in each arm at the specified time points have been presented. Pharmacokinetics (PK) population: All participants from whom a PK sample was obtained and analyzed. This population did not include participants from the control groups.

End point type

Secondary

End point timeframe

Day 1 (pre-dose), Week (Wk) 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	134	35
Units: nanograms per milliliter
arithmetic mean (standard deviation)
GSK1278863, Day 1, Pre-Dose, n=128, 35	0 ± 0	0 ± 0
GSK1278863, Wk 4, 6-12 hour Post-Dose, n=116, 31	2 ± 5.18	1.1 ± 1.69
GSK1278863, Wk 4, 7-13 hour Post-Dose, n=117, 31	2.3 ± 7.06	0.8 ± 1.22
GSK1278863, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.6 ± 4.93	1.6 ± 5.49
GSK1278863, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.4 ± 4.52	1.6 ± 4.6
GSK1278863, Wk 20, Pre-Dose, n=111, 29	0.6 ± 3.07	0.3 ± 0.92
GSK1278863, Wk 20, 1 hour Post-Dose, n=110, 28	22.8 ± 35.93	19.8 ± 19.66
GSK1278863, Wk 20, 2 hour Post-Dose, n=109, 29	17 ± 28.57	19.4 ± 21.92
GSK1278863, Wk 20, 3 hour Post-Dose, n=109, 29	11.6 ± 19.56	13.9 ± 19.12
GSK2391220, Day 1, Pre-Dose, n=128, 35	0 ± 0	0 ± 0
GSK2391220, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.2 ± 5.21	3.7 ± 2.89
GSK2391220, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.1 ± 5.67	3.2 ± 2.43
GSK2391220, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.8 ± 5.01	2.9 ± 2.54
GSK2391220, Wk 4, 9-15 hour Post-Dose, n=116, 31	2.6 ± 4.89	3.1 ± 2.76
GSK2391220, Wk 20, Pre-Dose, n=111, 29	1 ± 2.06	0.8 ± 0.98
GSK2391220, Wk 20, 1 hour Post-Dose, n=110, 28	2.1 ± 3.52	1.6 ± 1.39
GSK2391220, Wk 20, 2 hour Post-Dose, n=109, 29	3.8 ± 5.08	3.7 ± 2.98
GSK2391220, Wk 20, 3 hour Post-Dose, n=109, 29	4.5 ± 5.43	4.7 ± 3.53
GSK2487818, Day 1, Pre-Dose, n=128, 35	0 ± 0	0 ± 0
GSK2487818, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.2 ± 3.87	1 ± 0.96
GSK2487818, Wk 4, 7-13 hour Post-Dose, n=116, 31	1.1 ± 4.11	0.7 ± 0.7
GSK2487818, Wk 4, 8-14 hour Post-Dose, n=116, 31	1 ± 4.48	0.6 ± 0.66
GSK2487818, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.9 ± 4.09	0.8 ± 1.16
GSK2487818, Wk 20, Pre-Dose, n=111, 29	0.2 ± 0.56	0.1 ± 0.31
GSK2487818, Wk 20, 1 hour Post-Dose, n=110, 28	1.4 ± 3.07	1 ± 1.09
GSK2487818, Wk 20, 2 hour Post-Dose, n=109, 29	2.8 ± 4.28	2.7 ± 2.21
GSK2487818, Wk 20, 3 hour Post-Dose, n=109, 29	3.1 ± 4.07	3.1 ± 2.56
GSK2506102, Day 1, Pre-Dose, n=128, 35	0 ± 0	0 ± 0
GSK2506102, Wk 4, 6-12 hour Post-Dose, n=116, 31	1 ± 1.3	1.2 ± 0.65
GSK2506102, Wk 4, 7-13 hour Post-Dose, n=117, 31	1 ± 1.51	1.1 ± 0.61
GSK2506102, Wk 4, 8-14 hour Post-Dose, n=116, 31	0.9 ± 1.19	1 ± 0.61
GSK2506102, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.9 ± 1.29	1.1 ± 0.69
GSK2506102, Wk 20, Pre-Dose, n=111, 29	0.4 ± 0.73	0.4 ± 0.42
GSK2506102, Wk 20, 1 hour Post-Dose, n=110, 28	0.6 ± 0.88	0.5 ± 0.4
GSK2506102, Wk 20, 2 hour Post-Dose, n=109, 29	0.9 ± 1.15	1 ± 0.71
GSK2506102, Wk 20, 3 hour Post-Dose, n=109, 29	1.1 ± 1.25	1.2 ± 0.88
GSK2531398, Day 1, Pre-Dose, n=128, 35	0 ± 0.01	0 ± 0
GSK2531398, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.3 ± 2.06	1.4 ± 1.08
GSK2531398, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.2 ± 2.5	1.2 ± 0.99
GSK2531398, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.1 ± 2.01	1.1 ± 0.93
GSK2531398, Wk 4, 9-15 hour Post-Dose, n=116, 31	1 ± 2.1	1.2 ± 1.12
GSK2531398, Wk 20, Pre-Dose, n=111, 29	0.3 ± 0.87	0.3 ± 0.38
GSK2531398, Wk 20, 1 hour Post-Dose, n=110, 28	0.8 ± 1.53	0.6 ± 0.54
GSK2531398, Wk 20, 2 hour Post-Dose, n=109, 29	1.6 ± 2.31	1.5 ± 1.22
GSK2531398, Wk 20, 3 hour Post-Dose, n=109, 29	2 ± 2.42	2 ± 1.57
GSK2531401, Day 1, Pre-Dose, n=128, 35	0 ± 0	0 ± 0
GSK2531401, Wk 4, 6-12 hour Post-Dose, n=116, 31	2.8 ± 4	4.3 ± 2.55
GSK2531401, Wk 4, 7-13 hour Post-Dose, n=117, 31	2.7 ± 3.58	4 ± 2.29
GSK2531401, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.7 ± 3.74	3.8 ± 2.31
GSK2531401, Wk 4, 9-15 hour Post-Dose, n=116, 31	2.5 ± 3.53	3.8 ± 2.29
GSK2531401, Wk 20, Pre-Dose, n=111, 29	1.3 ± 2.41	1.4 ± 1.38
GSK2531401, Wk 20, 1 hour Post-Dose, n=110, 28	1.6 ± 2.65	1.6 ± 1.29
GSK2531401, Wk 20, 2 hour Post-Dose, n=109, 29	2.3 ± 3.14	2.5 ± 1.85
GSK2531401, Wk 20, 3 hour Post-Dose, n=109, 29	2.8 ± 3.5	3.2 ± 2.22
GSK2531403, Day 1, Pre-Dose, n=128, 35	0 ± 0	0 ± 0
GSK2531403, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.7 ± 5.43	4.5 ± 3.14
GSK2531403, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.5 ± 5.27	3.9 ± 2.56
GSK2531403, Wk 4, 8-14 hour Post-Dose, n=116, 31	3.4 ± 5.68	3.7 ± 2.72
GSK2531403, Wk 4, 9-15 hour Post-Dose, n=116, 31	3.2 ± 5.42	3.8 ± 3.01
GSK2531403, Wk 20, Pre-Dose, n=111, 29	1.4 ± 2.65	1.2 ± 1.25
GSK2531403, Wk 20, 1 hour Post-Dose, n=110, 28	2.3 ± 3.69	1.9 ± 1.38
GSK2531403, Wk 20, 2 hour Post-Dose, n=109, 29	3.9 ± 5.03	3.8 ± 2.95
GSK2531403, Wk 20, 3 hour Post-Dose, n=109, 29	4.7 ± 5.43	4.9 ± 3.75

No statistical analyses for this end point

Secondary: Mean number of dose adjustments up to 24 Weeks

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End point title

Mean number of dose adjustments up to 24 Weeks ^[11]

End point description

After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. Intent-to-Treat population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed.

End point type

Secondary

End point timeframe

From Week 4 up to 24 Weeks

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	102	26
Units: number of adjustments
arithmetic mean (standard deviation)	1.8 ± 0.82	1.7 ± 0.72

No statistical analyses for this end point

Secondary: Number of participants with dose adjustments up to 24 Weeks, as a measure of dose adjustment frequency

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End point title

Number of participants with dose adjustments up to 24 Weeks, as a measure of dose adjustment frequency ^[12]

End point description

After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. Frequency is presented as the number of participants with dose adjustment(s) once, twice, thrice, four times, or five times. Intent-to-Treat population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed.

End point type

Secondary

End point timeframe

From week 4 up to 24 weeks

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	102	26
Units: participants
number (not applicable)
Once	39	11
Twice	50	11
Thrice	8	4
Four times	4	0
Five times or more	1	0

No statistical analyses for this end point

Secondary: Timing of dose adjustments at Weeks 4, 8, 12, 16, and 20

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End point title

Timing of dose adjustments at Weeks 4, 8, 12, 16, and 20 ^[13]

End point description

After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. The number of participants with an adjustment are presented at the timings at which adjustments were done. ITT population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed.

End point type

Secondary

End point timeframe

From Week 4 up to Week 20

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	102	26
Units: Participants
number (not applicable)
Week 4	78	21
Week 8	24	6
Week 12	30	7
Week 16	30	6
Week 20	22	5

No statistical analyses for this end point

Secondary: Mean total cumulative dose of GSK1278863 up to 24 Weeks

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End point title

Mean total cumulative dose of GSK1278863 up to 24 Weeks ^[14]

End point description

The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. ITT population

End point type

Secondary

End point timeframe

Up to 24 Weeks

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	123	33
Units: milligrams
arithmetic mean (standard deviation)	249.75 ± 186.921	320.42 ± 214.865

No statistical analyses for this end point

Secondary: Mean final dose of GSK1278863 up to 24 Weeks

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End point title

Mean final dose of GSK1278863 up to 24 Weeks ^[15]

End point description

End point type

Secondary

End point timeframe

Up to 24 Weeks

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	123	33
Units: milligrams per day
arithmetic mean (standard deviation)	1.75 ± 1.809	1.86 ± 1.692

No statistical analyses for this end point

Secondary: Number of hemoglobin (Hgb) excursions

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End point title

Number of hemoglobin (Hgb) excursions

End point description

A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. Hgb cycle is calculated as two consecutive Hgb excursions in different directions. Completers Population: ITT participants who fully completed study without prematurely discontinuing study drug. Only participants with Hgb excursions were analyzed.

End point type

Secondary

End point timeframe

Up to 24 Weeks.

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	23	10	4	8
Units: number of excursions
number (not applicable)	26	10	4	9

No statistical analyses for this end point

Secondary: Number of hemoglobin (Hgb) cycles up to 24 Weeks

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End point title

Number of hemoglobin (Hgb) cycles up to 24 Weeks

End point description

A Hgb cycle is calculated as two consecutive Hgb excursions in different directions. A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. Completers population. Only participants with Hgb cycles were analyzed.

End point type

Secondary

End point timeframe

Up to 24 Weeks

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	3	0 ^[16]	0 ^[17]	0 ^[18]
Units: number of Hgb cycles
number (not applicable)	3

Notes
[16] - There were no subjects for analysis
[17] - There were no subjects for analysis
[18] - There were no subjects for analysis

No statistical analyses for this end point

Secondary: Number of dose cycles up to 24 Weeks

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End point title

Number of dose cycles up to 24 Weeks ^[19]

End point description

A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease). Completers population. Only participants with dose cycles were analyzed. Completers population.

End point type

Secondary

End point timeframe

Up to 24 weeks

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	1	0 ^[20]
Units: number
number (not applicable)	1

Notes
[20] - There were no subjects for analysis

No statistical analyses for this end point

Secondary: Number of participants with at least one hemoglobin (Hgb) excursion up to 24 Weeks.

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End point title

Number of participants with at least one hemoglobin (Hgb) excursion up to 24 Weeks.

End point description

A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. Completers population.

End point type

Secondary

End point timeframe

Up to 24 weeks

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	106	36	30	30
Units: participants
number (not applicable)	23	10	4	8

No statistical analyses for this end point

Secondary: Number of participants with at least one hemoglobin (Hgb) cycle up to 24 Weeks

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End point title

Number of participants with at least one hemoglobin (Hgb) cycle up to 24 Weeks

End point description

A Hgb excursion is a series of decreasing or increasing Hgb values differing by >=1.5 grams per deciliter. A Hgb cycle is two consecutive Hgb excursions in different directions. Completers population.

End point type

Secondary

End point timeframe

Up to 24 weeks

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	106	36	30	30
Units: participants
number (not applicable)	3	0	0	0

No statistical analyses for this end point

Secondary: Number of participants with at least one dose cycle up to 24 Weeks

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End point title

Number of participants with at least one dose cycle up to 24 Weeks ^[21]

End point description

End point type

Secondary

End point timeframe

Up to 24 weeks

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	106	30
Units: participants
number (not applicable)	1	0

No statistical analyses for this end point

Secondary: Number of participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO at any time post-Baseline

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End point title

Number of participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO at any time post-Baseline

End point description

Participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO any time Post Baseline were analyzed. RhEPO was not applicable for the control arms since it was a planned therapy in those arms, hence presented as NA. (EudraCT only: A value of 99999 is used where no data is available or NA.) ITT population.

End point type

Secondary

End point timeframe

From Day 1 up to Week 28

End point values	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Number of subjects analysed	123	43	33	36
Units: participants
number (not applicable)
Blood Transfusions	3	1	1	0
IV Iron	20	3	3	4
Inadvertent rhEPO use	4	99999	9	99999
Rescue rhEPO	1	99999	0	99999

No statistical analyses for this end point

Secondary: Number of Weeks dose withheld because hemoglobin (Hgb) exceeded the upper limit

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End point title

Number of Weeks dose withheld because hemoglobin (Hgb) exceeded the upper limit ^[22]

End point description

Number of Weeks dose was withheld because hemoglobin exceed the upper limit is presented as the number of participants with withheld dose during the time periods categorized by Weeks. ITT population.

End point type

Secondary

End point timeframe

From Week 4 up to Week 24

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There are no statistical analyses to report for this outcome measure.

End point values	rhEPO-Naive GSK1278863	rhEPO-User GSK1278863
Number of subjects analysed	123	33
Units: participants
number (not applicable)
0 Weeks	102	30
>0-4 Weeks	4	2
>4-8 Weeks	8	0
>8-12 Weeks	8	0
>12 Weeks	1	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (up to 28 weeks).

Adverse event reporting additional description

AEs and SAEs were collected from participants of the safety population, comprised of all participants who received at least one dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

rhEPO-Naive GSK1278863

Reporting group description

Reporting group title

rhEPO-Naive Control

Reporting group description

Reporting group title

rhEPO-User GSK1278863

Reporting group description

Reporting group title

rhEPO-User Control

Reporting group description

Serious adverse events	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Total subjects affected by serious adverse events
subjects affected / exposed	20 / 134 (14.93%)	6 / 45 (13.33%)	6 / 36 (16.67%)	7 / 35 (20.00%)
number of deaths (all causes)	2	0	2	1
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gallbladder adenocarcinoma
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
HEPATIC CANCER
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
DIABETIC VASCULAR DISORDER
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
HYPERTENSION
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
CHEST PAIN
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
CONFUSIONAL STATE
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
MENTAL STATUS CHANGES
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
FALSE POSITIVE INVESTIGATION RESULT
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Shunt malfunction
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
ANGINA PECTORIS
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ATRIOVENTRICULAR BLOCK COMPLETE
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC FAILURE CONGESTIVE
subjects affected / exposed	2 / 134 (1.49%)	1 / 45 (2.22%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
MYOCARDIAL ISCHAEMIA
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC FAILURE
subjects affected / exposed	0 / 134 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
CARPAL TUNNEL SYNDROME
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
NEURALGIA
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CEREBRAL MICROANGIOPATHY
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic encephalopathy
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
GASTRIC ULCER
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
SMALL INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
RECTAL HAEMORRHAGE
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
RENAL FAILURE CHRONIC
subjects affected / exposed	2 / 134 (1.49%)	2 / 45 (4.44%)	1 / 36 (2.78%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
GLOMERULONEPHRITIS CHRONIC
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
DIABETIC NEPHROPATHY
subjects affected / exposed	0 / 134 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
RENAL FAILURE
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
RENAL IMPAIRMENT
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
CHONDROCALCINOSIS PYROPHOSPHATE
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Biliary sepsis
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	1 / 134 (0.75%)	1 / 45 (2.22%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
PYELONEPHRITIS CHRONIC
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
APPENDICITIS
subjects affected / exposed	0 / 134 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CELLULITIS
subjects affected / exposed	0 / 134 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA PNEUMOCOCCAL
subjects affected / exposed	0 / 134 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 134 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
HYPOKALAEMIA
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
FLUID OVERLOAD
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
HYPOGLYCAEMIA
subjects affected / exposed	1 / 134 (0.75%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gout
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control
Total subjects affected by non serious adverse events
subjects affected / exposed	47 / 134 (35.07%)	14 / 45 (31.11%)	20 / 36 (55.56%)	13 / 35 (37.14%)
Investigations
BLOOD PRESSURE INCREASED
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences all number	1	0	2	3
Vascular disorders
HYPERTENSION
subjects affected / exposed	2 / 134 (1.49%)	1 / 45 (2.22%)	4 / 36 (11.11%)	1 / 35 (2.86%)
occurrences all number	3	1	6	1
General disorders and administration site conditions
OEDEMA PERIPHERAL
subjects affected / exposed	5 / 134 (3.73%)	0 / 45 (0.00%)	2 / 36 (5.56%)	3 / 35 (8.57%)
occurrences all number	3	0	2	3
ASTHENIA
subjects affected / exposed	1 / 134 (0.75%)	3 / 45 (6.67%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences all number	1	3	1	0
FATIGUE
subjects affected / exposed	3 / 134 (2.24%)	1 / 45 (2.22%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences all number	3	1	1	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 134 (0.00%)	1 / 45 (2.22%)	3 / 36 (8.33%)	0 / 35 (0.00%)
occurrences all number	0	1	3	0
Gastrointestinal disorders
DIARRHOEA
subjects affected / exposed	10 / 134 (7.46%)	0 / 45 (0.00%)	0 / 36 (0.00%)	6 / 35 (17.14%)
occurrences all number	10	0	0	6
NAUSEA
subjects affected / exposed	8 / 134 (5.97%)	1 / 45 (2.22%)	1 / 36 (2.78%)	0 / 35 (0.00%)
occurrences all number	10	1	2	0
CONSTIPATION
subjects affected / exposed	5 / 134 (3.73%)	1 / 45 (2.22%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences all number	5	1	1	2
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
subjects affected / exposed	3 / 134 (2.24%)	0 / 45 (0.00%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences all number	3	0	1	2
Skin and subcutaneous tissue disorders
PRURITUS
subjects affected / exposed	0 / 134 (0.00%)	4 / 45 (8.89%)	0 / 36 (0.00%)	0 / 35 (0.00%)
occurrences all number	0	4	0	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	2 / 134 (1.49%)	2 / 45 (4.44%)	1 / 36 (2.78%)	3 / 35 (8.57%)
occurrences all number	2	2	1	3
BACK PAIN
subjects affected / exposed	1 / 134 (0.75%)	1 / 45 (2.22%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences all number	1	1	1	2
Infections and infestations
NASOPHARYNGITIS
subjects affected / exposed	15 / 134 (11.19%)	2 / 45 (4.44%)	7 / 36 (19.44%)	2 / 35 (5.71%)
occurrences all number	17	2	8	2
CONJUNCTIVITIS
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	2 / 36 (5.56%)	0 / 35 (0.00%)
occurrences all number	1	0	2	0
Bronchitis
subjects affected / exposed	2 / 134 (1.49%)	1 / 45 (2.22%)	0 / 36 (0.00%)	3 / 35 (8.57%)
occurrences all number	2	1	0	3
Metabolism and nutrition disorders
GOUT
subjects affected / exposed	2 / 134 (1.49%)	0 / 45 (0.00%)	1 / 36 (2.78%)	2 / 35 (5.71%)
occurrences all number	3	0	1	2
HYPERKALAEMIA
subjects affected / exposed	2 / 134 (1.49%)	0 / 45 (0.00%)	2 / 36 (5.56%)	1 / 35 (2.86%)
occurrences all number	3	0	2	1
Hypoglycaemia
subjects affected / exposed	1 / 134 (0.75%)	0 / 45 (0.00%)	2 / 36 (5.56%)	1 / 35 (2.86%)
occurrences all number	3	0	2	1

More information

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Were there any global substantial amendments to the protocol? Yes

12 Sep 2013

To revise the GSK1278863 Dose Adjustment Algorithm as requested by the United States FDA and to clarify and correct language throughout.

03 Oct 2013

Amendment for Japan only. To revise the Time and Events Table (Table 3) to add a HemoCue and Quest Hgb assessment at Week 2 as requested by PMDA.

23 Jan 2014

To revise lipid and biomarker assessments, to add reconfirmation of the QTc inclusion criterion at Day 1, to remove requirement for male contraception, to allow an interim cut of data to be taken to facilitate dose modelling, and to make minor clarifications throughout.

04 Feb 2014

Document version number change only: Change in document number because an error was found after publishing Amendment 03, but before distribution. The error was corrected and the document republished with a new document number.

08 May 2014

To change the Hgb entry criteria and target range for countries outside of the United States, to change the TSAT entry criterion, to clarify that subject who are not able to complete quality of life scales without assistance should not complete the scales, to change to the name of the rhEPO group (now called “the Control arm”) as well as to clarify how subjects in the Control arm are to be managed; to make minor clarifications to the analysis section and throughout the document.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A 24-week, Phase IIB, Randomized, Controlled, Parallel group, Multi-center Study to Evaluate the Safety and Efficacy of GSK1278863 in Subjects with Anemia Associated with Chronic Kidney Diseases who are not on Dialysis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Summary of hemoglobin (Hgb) concentration at Week 24

Primary: Summary of hemoglobin (Hgb) concentration at Week 24

Secondary: Number of participants with hemoglobin (Hgb) in the target range at Week 24

Secondary: Number of participants with hemoglobin (Hgb) in the target range at Week 24

Secondary: Number of participants reaching pre-defined Hgb stopping criteria

Secondary: Number of participants reaching pre-defined Hgb stopping criteria

Secondary: Percent change from Baseline in hepcidin concentration at Week 24

Secondary: Percent change from Baseline in hepcidin concentration at Week 24

Secondary: Maximum observed change from Baseline in serum erythropoietin (EPO)

Secondary: Maximum observed change from Baseline in serum erythropoietin (EPO)

Secondary: Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)

Secondary: Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)

Secondary: Percentage of time within, below, and above hemoglobin (Hgb) target range, between Weeks 12 and 24

Secondary: Percentage of time within, below, and above hemoglobin (Hgb) target range, between Weeks 12 and 24

Secondary: Change from Baseline in ferritin concentration at Week 24

Secondary: Change from Baseline in ferritin concentration at Week 24

Secondary: Change from Baseline in transferrin concentration at Week 24

Secondary: Change from Baseline in transferrin concentration at Week 24

Secondary: Percent change from Baseline in transferrin saturation at Week 24

Secondary: Percent change from Baseline in transferrin saturation at Week 24

Secondary: Change from Baseline in total iron at Week 24

Secondary: Change from Baseline in total iron at Week 24

Secondary: Change from Baseline in total iron binding capacity (TIBC) at Week 24

Secondary: Change from Baseline in total iron binding capacity (TIBC) at Week 24

Secondary: Change from Baseline in reticulocyte hemoglobin (CHr) at Week 24

Secondary: Change from Baseline in reticulocyte hemoglobin (CHr) at Week 24

Secondary: Change from Baseline in hematocrit at Week 24

Secondary: Change from Baseline in hematocrit at Week 24

Secondary: Change from Baseline in red blood cell count at Week 24

Secondary: Change from Baseline in red blood cell count at Week 24

Secondary: Change from Baseline in reticulocyte cell count at Week 24

Secondary: Change from Baseline in reticulocyte cell count at Week 24

Secondary: Concentration of GSK1278863 and relevant metabolites as a population pharmacokinetic endpoint

Secondary: Concentration of GSK1278863 and relevant metabolites as a population pharmacokinetic endpoint

Secondary: Mean number of dose adjustments up to 24 Weeks

Secondary: Mean number of dose adjustments up to 24 Weeks

Secondary: Number of participants with dose adjustments up to 24 Weeks, as a measure of dose adjustment frequency

Secondary: Number of participants with dose adjustments up to 24 Weeks, as a measure of dose adjustment frequency

Secondary: Timing of dose adjustments at Weeks 4, 8, 12, 16, and 20

Secondary: Timing of dose adjustments at Weeks 4, 8, 12, 16, and 20

Secondary: Mean total cumulative dose of GSK1278863 up to 24 Weeks

Secondary: Mean total cumulative dose of GSK1278863 up to 24 Weeks

Secondary: Mean final dose of GSK1278863 up to 24 Weeks

Secondary: Mean final dose of GSK1278863 up to 24 Weeks

Secondary: Number of hemoglobin (Hgb) excursions

Secondary: Number of hemoglobin (Hgb) excursions

Secondary: Number of hemoglobin (Hgb) cycles up to 24 Weeks

Secondary: Number of hemoglobin (Hgb) cycles up to 24 Weeks

Secondary: Number of dose cycles up to 24 Weeks

Secondary: Number of dose cycles up to 24 Weeks

Secondary: Number of participants with at least one hemoglobin (Hgb) excursion up to 24 Weeks.

Secondary: Number of participants with at least one hemoglobin (Hgb) excursion up to 24 Weeks.

Secondary: Number of participants with at least one hemoglobin (Hgb) cycle up to 24 Weeks

Secondary: Number of participants with at least one hemoglobin (Hgb) cycle up to 24 Weeks

Secondary: Number of participants with at least one dose cycle up to 24 Weeks

Secondary: Number of participants with at least one dose cycle up to 24 Weeks

Secondary: Number of participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO at any time post-Baseline

Secondary: Number of participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO at any time post-Baseline

Secondary: Number of Weeks dose withheld because hemoglobin (Hgb) exceeded the upper limit

Secondary: Number of Weeks dose withheld because hemoglobin (Hgb) exceeded the upper limit

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A 24-week, Phase IIB, Randomized, Controlled, Parallel group, Multi-center Study to Evaluate the Safety and Efficacy of GSK1278863 in Subjects with Anemia Associated with Chronic Kidney Diseases who are not on Dialysis.